Loxosceles reclusa (the poisonous brown recluse spider) is the causative agent of severe necrotizing wounds which develop following the spider bite. The bite has occasionally produced a massive intravascular homolysis and thrombocytopenia. Among the host responses induced by the venom which may contribute to lesion development are red blood cell lysis, inactivation of serum complement, dermonecrosis, and chemotaxis of leukocytes. These observations indicate that the spider venom contains a combination of unique toxic agents. It is the purpose of this proposal to identify these agents and to characterize them in terms of their biochemical and immunologic properties. We also propose to determine how these toxic agents act in concert to produce the pathological consequences of the spider bite. With such information we intend to devise therapeutic procedures to avoid lesion development.